Seronegative myasthenia gravis: disease severity and prognosis

Abstract

Around 10-20% of myasthenia gravis (MG) patients do not have acetylcholine receptor (AChR) antibodies (seronegative), of whom some have antibodies to a membrane-linked muscle specific kinase (MuSK). To examine MG severity and long-term prognosis in seronegative MG compared with seropositive MG, and to look specifically at anti-AChR antibody negative and anti-MuSK antibody negative patients. Seventeen consecutive seronegative non-thymomatous MG patients and 34 age and sex matched contemporary seropositive non-thymomatous MG controls were included in a retrospective follow-up study for a total period of 40 years. Clinical criteria were assessed each year, and muscle antibodies were assayed. There was no difference in MG severity between seronegative and seropositive MG. However, when thymectomized patients were excluded from the study at the year of thymectomy, seropositive MG patients had more severe course than seronegative (P < 0.001). One seropositive patient died from MG related respiratory insufficiency. The need for thymectomy in seronegative MG was lower than in seropositive MG. None of the seronegative patients had MuSK antibodies. This study shows that the presence of AChR antibodies in MG patients correlates with a more severe MG. With proper treatment, especially early thymectomy for seropositive MG, the outcome and long-term prognosis is good in patients with and without AChR antibodies.

Geographical Distribution of Myasthenia Gravis in Northern Europe - Results from a Population-Based Study from Two Countries

“…There is, however, a consistent trend toward more MuSK MG patients in the seronegative cohorts at southern latitudes, which support our findings. Our finding of only two MuSK MG patients in Norway is consistent with the report of zero Norwegian MuSK MG patients by Romi et al in a case series of 19 seronegative MG patients [14] . The increase in MuSK prevalence in the Netherlands from 2.8 in 2004 to 6.5 in 2012 cannot be explained by incident cases and longevity alone [16] .…”

“…However, findings such as female predominance and increasing incidence of late-onset MG (LOMG) are persistent worldwide [10][11][12][13] . Previous studies postulate a latitudinal north-south gradient of the MuSK MG prevalence in Europe, being low in the north and higher in the Mediterranean countries [14][15][16][17][18] . However, the only two population-based studies calculating the prevalence of MuSK MG do not show a difference between the Mediterranean country of Greece and the Netherlands in northern Europe [16,19] .…”

Comparison of muscle ultrastructure in myasthenia gravis with anti-MuSK and anti-AChR antibodies

“…MuSK is essential for the formation of the NMJ during embryonic life, but remains important after birth for the maturation and/or maintenance of the adult neuromuscular synapse. MuSK-MG presents three main clinical patterns: the first type involves severe oculobulbar weakness and profound tongue and facial atrophy, the second type has predominant neck, shoulder, and respiratory muscle involvement but without ocular weakness, while the third type is similar to AChR-MG. MuSK-MG is less responsive to acetylcholinesterase therapy, the response to thymectomy is unclear and might need higher drug dosages than AChR-MG [10][11][12]. A few MuSK-MG patients present prominent muscle atrophy and a myopathic pattern on electromyography [13].…”

Efficacy of immunotherapy in seropositive and seronegative putative autoimmune autonomic ganglionopathy

“…This suggests the need to treat patients with AAG phenotype even if seronegative for ganglionic AChR antibodies, as occurs in other autoimmune neurologic disorders like myasthenia gravis. 20,21 In our patients, improvement in symptoms and deficits occurred with treatment with considerable heterogeneity in pattern of response. Some patients with AAG, whether seropositive or seronegative, respond to treatment with IVIg or PE, although when used as a single agent, subsequent treatments are required in most relapsing patients to maintain the improvement.…”